: NESAC/BIO provides the biomedical research community with state-of-the-art surface analysis expertise, instrumentation, experimental protocols, and data analysis methods to address biological and medical problems involving the surface and interfacial regions. Since the nature of the surface strongly influences the composition and recognizability of the biomolecules and cells that interact with materials, understanding the structure of surfaces and the nature of adsorbed biomolecules are key links in understanding interfacial biology for both in vivo (e.g., implanted biomedical devices) and in vitro (e.g., DNA microarrays) applications. ESCA, ToF-SIMS, SPM, and SFG provide a powerful set of complementary techniques for addressing the challenges and complexity of the new generation of biomaterials and devices being developed. Each technique has its strengths and weaknesses for biomedical surface analysis, but together they provide a detailed and comprehensive understanding of biomedical surface structure and composition. Many of these materials and devices have patterned surfaces and/or multi-phase structures, which requires 2-D or 3-D imaging for spatially resolved chemical analysis. The Technology Research and Development (TR&D) projects are: (1) Surface Mass Spectrometry Technique & Analysis Development, (2) SIMS of Cells & Tissues (3) Characterization of Nanoparticles and (4) Biomolecules at Interfaces. Development of methods for 3D analysis of cells and tissues, as well as biomolecules interactions with flat and nanoparticle surfaces will be a focus for the next five years. The Collaborative Research projects drive the TR&D method development as well as presenting important biomedical research problems that require state-of-the-art surface analysis techniques. NESAC/BIO Service activities will focus on providing ESCA and ToF-SIMS surface analysis data and reports to biomedical research community. Dissemination (presentations, publications, website, etc.) and Training projects (workshops, courses, one-on-one instruction, etc.) are also key parts of the NESAC/BIO program.